Cure Parkinson’s and Van Andel Institute (VAI) are delighted to announce funding for an upcoming phase 1b clinical trial to investigate whether lithium, a drug currently used to treat mood disorders, could be repurposed to slow down Parkinson’s.

Lithium has been used to treat bipolar disorder since the 1960’s due to its mood-stabilising effects and recently researchers have started looking into it as a possible treatment for Parkinson’s.

Cure Parkinson’s and VAI will fund the recruitment of 20 people with Parkinson’s to the upcoming clinical trial of low-dose lithium, led by Dr Thomas Guttuso at the University of Buffalo. This is in addition to 15 people with Parkinson’s already funded by the US National Institutes of Health (NIH), bringing the total group to 35 participants. The main objective of the researchers is to find out if lithium changes two specific signs of Parkinson’s: the amount of a protein called Nurr1 in the blood, and levels of ‘free water’ in the brain. These are known as biomarkers and they are important because they help researchers understand what’s happening in the brain without directly accessing it.

What is Nurr1 and Free Water?

‘Nuclear receptor related 1 protein’ (Nurr1) is a molecule that plays a vital role in the creation of new dopamine neurons, the type of cells that are progressively lost in Parkinson’s. Although Nurr1 levels decrease naturally with age, evidence suggests that Nurr1 levels are even lower in people with Parkinson’s. In the 2019 pilot study, low-dose lithium was found to increase Nurr1 levels, which may promote dopamine neuron survival in people with Parkinson’s, therefore potentially slowing disease progression.

Increased levels of ‘free water’ in the brain, measured via brain imaging techniques, can be used as a marker of dopamine neuron loss in Parkinson’s. Free water refers to fluids in the brain that are not bound in cells. The 2019 pilot study of lithium in Parkinson’s suggested that low-dose lithium may be able to reduce this free water increase in the brain; the phase 1 study will look to replicate this finding in a larger cohort of people with Parkinson’s.

Because brain ‘free water’ is one of our leading disease-progression biomarkers in Parkinson’s, if this study is able to replicate our earlier findings associating low-dose lithium therapy with reductions in free water, this would support low-dose lithium’s ability to slow Parkinson’s progression and also strongly support further clinical research using this simple and inexpensive therapy. Positive effects on one or more blood-based biomarkers, including Nurr1, would further bolster this research program.

Dr Thomas Guttuso, University at Buffalo, Principal Investigator

Why study lithium in Parkinson’s?

Early laboratory research suggests that lithium at very low doses may help protect against the loss of dopamine nerve cells (neurons) seen in Parkinson’s. In 2019, Dr Guttuso conducted a small pilot study to explore this potential benefit in people with Parkinson’s. The results were promising, indicating that lithium had a positive effect on the trial participants. Because of this, in 2022, low-dose lithium was prioritised by the International Linked Clinical Trials (iLCT) programme – a drug development initiative set up in partnership between Cure Parkinson’s and VAI to support the testing of drugs with the potential to slow or stop Parkinson’s.

Overall, the trial aims to provide the information needed to determine whether low-dose lithium should continue to be further tested in clinical trials for Parkinson’s.

Parkinson’s is an immensely complex disorder that requires an equally sophisticated approach to seeking treatments that slow or stop progression. International Linked Clinical Trials enables us to prioritize medications like lithium that are known to treat other diseases and that may have use in Parkinson’s. This phase 1b trial will be an important step in evaluating lithium’s potential use in impeding disease progression, and we look forward to the results.

Dr Darren Moore, chair of VAI’s Department of Neurodegenerative Science and member of the iLCT Committee

Research reported in this publication is supported in part by the US National Center for Advancing Translational Sciences of the National Institutes of Health under award no. UL1TR001412. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health or other funders.

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